chr6-111720156-T-G

Variant names:

• chr6-111720156-T-G
• rs706895
• NM_002037.5:c.-11-94A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002037.5(FYN):​c.-11-94A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000785 in 1,273,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 0 publications found

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	NM_002037.5	MANE Select	c.-11-94A>C		intron	N/A	NP_002028.1	P06241-1
	FYN	NM_001370529.1		c.-11-94A>C		intron	N/A	NP_001357458.1	P06241-1
	FYN	NM_153047.4		c.-11-94A>C		intron	N/A	NP_694592.1	P06241-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.-11-94A>C		intron	N/A	ENSP00000346671.3	P06241-1
	FYN	ENST00000229471.8	TSL:1	c.-11-94A>C		intron	N/A	ENSP00000229471.4	P06241-3
	FYN	ENST00000905552.1		c.-11-94A>C		intron	N/A	ENSP00000575611.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.85e-7 AC: 1 AN: 1273670 Hom.: 0 AF XY: 0.00000161 AC XY: 1 AN XY: 621928

African (AFR) AF: 0.00 AC: 0 AN: 28580

American (AMR) AF: 0.00 AC: 0 AN: 24468

Ashkenazi Jewish (ASJ) AF: 0.0000525 AC: 1 AN: 19050

East Asian (EAS) AF: 0.00 AC: 0 AN: 36486

South Asian (SAS) AF: 0.00 AC: 0 AN: 63460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998872

Other (OTH) AF: 0.00 AC: 0 AN: 53050

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		-1.3
PromoterAI		-0.0034	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs706895; hg19: chr6-112041359;